Robust evaluation of longitudinal surrogate markers with censored data
提出稳健方法评估纵向替代标志物在删失时间-事件结局中的表现，通过糖尿病预防项目数据验证空腹血糖作为替代标志物的效果。
Abstract The development of statistical methods to evaluate surrogate markers is an active area of research. In many clinical settings, the surrogate marker is not simply a single measurement but is instead a longitudinal trajectory of measurements over time, e.g. fasting plasma glucose measured every 6 months for 3 years. In general, available methods developed for the single-surrogate setting cannot accommodate a longitudinal surrogate marker. Furthermore, many of the methods have not been developed for use with primary outcomes that are time-to-event outcomes and/or subject to censoring. In this paper, we propose robust methods to evaluate a longitudinal surrogate marker in a censored time-to-event outcome setting. Specifically, we propose a method to define and estimate the proportion of the treatment effect on a censored primary outcome that is explained by the treatment effect on a longitudinal surrogate marker measured up to time t0. We accommodate both potential censoring of the primary outcome and of the surrogate marker. A simulation study demonstrates a good finite-sample performance of our proposed methods. We illustrate our procedures by examining repeated measures of fasting plasma glucose, a surrogate marker for diabetes diagnosis, using data from the diabetes prevention programme.